Dr Rebecca Goss Bio and Abstract

Dr Rebecca Goss is interested in the biosynthesis of natural products and in how these biosynthetic pathways may be harnessed in order to generate new designer natural products. For analogue generation, this approach can prove more expeditious that total synthesis.

Dr Goss completed her undergraduate studies in Chemistry at the University of Durham between 1994-1997. A PhD was then carried out into the biosynthesis of various natural products including the stereochemistry of enzymatic fluorination in fluoroacetate biosynthesis under the supervision of Professor David O’Hagan (University of Durham, awarded 2001). In 2000 Dr Goss moved to the University of Cambridge to study the chemistry and molecular biology of polyketide biosynthesis in the research group of Professors Jim Staunton FRS and Peter Leadlay FRS. In 2002, Dr Goss moved to an independent position within the department of Chemistry at the University of Nottingham. Following the award of a Royal Society BP Dorothy Hodgkin Fellowship in 2003 she moved to the University of Exeter. The Goss research group then moved to the University of East Anglia in 2005, where she was promoted to Reader. In 2012 Dr Goss moved to a Readership at the University of St Andrews.

In 2007 Dr Goss was awarded the RSC Meldola prize for her excellent contributions at the interface of organic chemistry and molecular biology. In 2013 she was awarded the Natural Product Report Emerging Researcher Lectureship (subsequently awarded to scientists at Yale then Harvard), for her pioneering new approach to natural product analogue generation “Genochemetics”, which marries together Synthetic Biology and Synthetic Chemistry to access new bioactives of medicinal interest. In 2014 she was awarded an ERC consolidator grant.

Elucidating and Exploiting Natural Product Biosynthesis

Rebecca J. M. GossSchool of Chemistry, University of St Andrews, Fife, Scotland, KY169ST UK

Though natural products represent a treasure trove of medicinally relevant compounds, they are commonly misperceived to be unsuitable for medicinal chemistry. We are developing new approaches to natural product analogue synthesis by blending together synthetic biology and synthetic chemistry. By complementing the biosynthetic machinery encoding an existing natural product with foreign genes we are able to introduce chemically orthogonal, reactive and selectable functionalisable handles into natural products. We have been developing mild chemical methodologies to enable the chemical derivitisation of these handles

Genochemetics: gene insertion enables the installation of a reactive and chemically orthogonal handle into a natural product, permitting its selective functionalization and diversification

References

1. Gene expression enabling synthetic diversification of unnatural products:chemogenetic generation pacidamycin analogs, A. Deb Roy, S. Grüschow, N. Cairns, R. J. M. Goss*, J. Am. Chem. Soc., 2010, 134, 1224-12245.

2. The Generation of “unNatural” Products, Combined Synthetic and Biosynthetic Approaches to Making Natural Product Analogues: Synthetic Biology Meets Synthetic Chemistry, R. J. M. Goss,* S. Shankar, and A. Abou Fayad, Nat. Prod. Rep., 2012, 29, 870-889

3. Natural Products: Discourse, Diversity and Design. A. E. Osbourn, G. Carter, and R. J. M. Goss, Wiley-Blackwell, 2014, ISBN: 978-1-118-29806-0

4. Awaking sleeping biosynthetic pathways: an overview of the main approaches used in coercing microbial biosynthetic gene clusters to reveal their natural products.J. Zarins Tutt, H. Gao, L. Zhang, A. M. Sprague, D. Newman and R. J. M. Goss* Nat. Prod. Rep., 2016, 33, 54-72.

5. Sonogashira diversification of unprotected halotryptophans, halotryptophans containing tripeptides and a new to nature bromometabolite in water, M. J. Corr, S. Sharma,

C. Pubill-Ulldemolins, R. T. Bown, P. Poirrot, D. R. M. Smith, C. Cartmell, T. Abou Fayad, R. J. M. Goss, ChemSci, 2016, in press